LncRNA MIAT facilitated BM-MSCs differentiation into endothelial cells and restored erectile dysfunction via targeting miR-200a in a rat model of erectile dysfunction

Wang, Hui; Ding, Xiegang; Yang, Jinjian; Li, Shiwen; Zheng, Hua; Li, Zhuoshi; Jia, Zhang; Li, Lü

doi:10.1016/j.ejcb.2018.02.001

Cited by 29 publications

(27 citation statements)

References 24 publications

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“…28 Another study has also elucidated the regulatory role of bone-marrow derived MSCs implantation in effectively restoring ED. 29 Moreover, exosomes secreted by adipose-derived stem cells has been associated with the attenuation of ED in T2DM rat models. 30 In addition, human MSCs-secreted exosomes were also found to alleviate T2DM.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells‐derived exosomal microRNA‐21‐5p downregulates PDCD4 and ameliorates erectile dysfunction in a rat model of diabetes mellitus

Huo

Zhang

et al. 2020

FASEB j.

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Erectile dysfunction (ED) is a common comorbidity in males with diabetes mellitus (DM), whose pathogenesis might be induced by dysregulation of corpus cavernosum smooth muscle cells (CCSMCs). Gene Expression Omnibus repository‐based analysis identified the differentially expressed PDCD4 in DM rats. PDCD4 has also been determined as a putative gene under the regulatory control of microRNA‐21‐5p (miR‐21‐5p). This study aimed to further determine the functional role of miR‐21‐5p in CCSMCs in a rat model of diabetes mellitus‐induced erectile dysfunction (DMED). CCSMCs were isolated from penile cavernous tissue and cultured in high glucose (HG) medium. The expression of miR‐21‐5p and/or PDCD4 was altered in CCSMCs, as directly or indirectly measured by CCK‐8 assay, flow cytometry, and TUNEL assays. Furthermore, exosomes were isolated from mesenchymal stem cells (MSCs) transfected with miR‐21‐5p mimic or miR‐21‐5p inhibitor and co‐cultured with CCSMCs. DMED rats were injected with lentivirus carrying PDCD4/siRNA‐PDCD4 plasmids, or exosomes from MSCs containing miR‐21‐5p‐agomir to explore their roles in vivo. The experimental data validated that PDCD4 was upregulated in cavernous tissue of DMED rats. miR‐21‐5p targeted and inhibited PDCD4. miR‐21‐5p was enriched in MSC‐exosomes. Moreover, PDCD4 downregulation, miR‐21‐5p elevation or MSC‐derived exosomal miR‐21‐5p reduced apoptosis and enhanced proliferation of CCSMCs cultured in HG medium. PDCD4 silencing or miR‐21‐5p‐containing MSC‐exosomes improved erectile function and smooth muscle density in DMED rats. Collectively, our findings suggested that MSC‐derived exosomal miR‐21‐5p suppressed PDCD4 expression and ED in rats with DM.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells‐derived exosomal microRNA‐21‐5p downregulates PDCD4 and ameliorates erectile dysfunction in a rat model of diabetes mellitus

Huo

Zhang

et al. 2020

FASEB j.

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“…As an example, MSCs can differentiate into endotheliocytes and myocytes in the mesoderm under conditional induction [84]. MSC-derived lncRNAs have been shown to support angiogenesis through the endothelial differentiation of MSCs: myocardial infarction-associated transcript (MIAT) targets miR200a and VEGF [85,86]; maternally expressed gene 3 (MEG3) facilitates the ubiquitination and degradation of forkhead box protein M1 (FOXM1) reducing the angiogenic VEGF expression and promoting endothelial differentiation of MSCs [87].…”

Section: Ev-associatedmentioning

confidence: 99%

Paracrine Mechanisms of Mesenchymal Stromal Cells in Angiogenesis

Maacha

Sidahmed²,

Jacob

et al. 2020

Stem Cells International

176

131

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The role of the mesenchymal stromal cell- (MSC-) derived secretome is becoming increasingly intriguing from a clinical perspective due to its ability to stimulate endogenous tissue repair processes as well as its effective regulation of the immune system, mimicking the therapeutic effects produced by the MSCs. The secretome is a composite product secreted by MSC in vitro (in conditioned medium) and in vivo (in the extracellular milieu), consisting of a protein soluble fraction (mostly growth factors and cytokines) and a vesicular component, extracellular vesicles (EVs), which transfer proteins, lipids, and genetic material. MSC-derived secretome differs based on the tissue from which the MSCs are isolated and under specific conditions (e.g., preconditioning or priming) suggesting that clinical applications should be tailored by choosing the tissue of origin and a priming regimen to specifically correct a given pathology. MSC-derived secretome mediates beneficial angiogenic effects in a variety of tissue injury-related diseases. This supports the current effort to develop cell-free therapeutic products that bring both clinical benefits (reduced immunogenicity, persistence in vivo, and no genotoxicity associated with long-term cell cultures) and manufacturing advantages (reduced costs, availability of large quantities of off-the-shelf products, and lower regulatory burden). In the present review, we aim to give a comprehensive picture of the numerous components of the secretome produced by MSCs derived from the most common tissue sources for clinical use (e.g., AT, BM, and CB). We focus on the factors involved in the complex regulation of angiogenic processes.

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“…The treatment with ARBs causes an upregulation of ACE2 as seen from animal studies 20,25,43 The angiotensin II type 1 receptor (AT1R) is the main receptor mediating angiotensin II effects. Losartan is angiotensin II type 1 receptor antagonists that demonstrate lung protectiveness.…”

Section: (I) Angiotensin Converting Enzyme (Ace) Inhibitorsmentioning

confidence: 99%